Quantitative Assessment of the Tension-Type Headache and Migraine Severity Continuum

Two quantitative measures for Waters'¹ tension-type head ache and migraine severity continuum are proposed. To ensure face validity, symptoms and precipitants of this disorder were compiled from the literature as a basis for the Auckland Migraine and Headache Inventory. This inventory was completed by 84 participants (mean age ± SD, 26.0 ± 9.7 years; range, 18 to 59 years) who complied with the criteria of the International Headache Society, for migraine of tension-type headache. The migraine headache index and the number of precipitants were derived from the Auckland Migraine and Headache Inventory. These scores yielded significant internal reliability ( r _s =.77 and .84), test-retest reliability ( r _s =.86 and .74), and concurrent validity ( r _s =.57) coefficients. The data, therefore, support the notion that the migraine headache index and the number of precipitants are reliable and valid indices of tension-type headache and migraine severity, suitable for participant selection and assessment of treatment. This study offers support for Waters'1 suggestion that tension-type headache and migraine are extremes of a severity continuum.     

MRI Findings in a Case of Ophthalmoplegic Migraine

SYNOPSIS
MRI using gadolinium contrast material can demonstrate lesions in cranial nerves. Tumors and Inflammatory lesions have been described.^1,2 There is little published information on MRI of cranial nerve in patients with migraine headache with ophthalmoplegia.³ We present a case of ophthalmoplegic migraine with a cranial nerve abnormality which was subsequently shown to improve as the patient clinically improved. Implications from this finding are discussed in relation to the pathophysiology of ophthalmoplegic migraine.     

Vasoactive intestinal peptide causes marked cephalic vasodilation, but does not induce migraine

We hypothesized that intravenous infusion of the parasympathetic transmitter, vasoactive intestinal peptide (VIP), might induce migraine attacks in migraineurs. Twelve patients with migraine without aura were allocated to receive 8 pmol kg⁻¹ min⁻¹ VIP or placebo in a randomized, double-blind crossover study. Headache was scored on a verbal rating scale (VRS), mean blood flow velocity in the middle cerebral artery ( V _{mean MCA}) was measured by transcranial Doppler ultrasonography, and diameter of the superficial temporal artery (STA) by high-frequency ultrasound. None of the subjects reported a migraine attack after VIP infusion. VIP induced a mild immediate headache (maximum 2 on VRS) compared with placebo ( P  = 0.005). Three patients reported delayed headache (3–11 h after infusion) after VIP and two after placebo ( P  = 0.89). V _{mean MCA} decreased (16.3 ± 5.9%) and diameter of STA increased significantly after VIP (45.9 ± 13.9%). VIP mediates a marked dilation of cranial arteries, but does not trigger migraine attacks in migraineurs. These data provide further evidence against a purely vascular origin of migraine.     

Sumatriptan Prophylaxis for Postelectroconvulsive Therapy Headaches

Very little has been written about headaches following electroconvulsive therapy (ECT) but the incidence has been estimated at 26%. ¹ Patients with a history of migraine occasionally have similar headaches precipitated by ECT.² In addition, some patients may have headaches that persist for months after a series of ECT treatments, while some patients who have a preexisting headache problem report improvement with ECT.³
Serotonergic mechanisms have been proposed both for the efficacy of ECT and its tendency to produce headaches in susceptible patients.^3,4 There have been no studies on the prophylaxis or treatment of post-ECT headache. While various strategies have been suggested for these headaches, even case reports documenting the efficacy of these strategies are lacking. We, therefore, report a case of severe, refractory, post-ECT headaches which responded to prophylactic treatment with sumatriptan.     

Toward a Standard Drug Formulary for the Treatment of Headache

The recent publication of drug formularies by third-party payers has serious implications for the practice of medicine. These formularies list the medications for which the consumer can be reimbursed by the third-party payer. The most restrictive of the five formularies I have received lists only two agents for the treatment of migraine headaches: Cafergot (at an incorrect dose of 1/100 mg) and Ergotrate which is no longer available. The most liberal of the formularies lists analgesics, Cafergot, Midrin, and Imitrex for the treatment of acute attacks, and as prophylactic agents, Inderal, Sansert, and analgesics (known to cause rebound headaches when used in this fashion in migraine patients). Abortive agents of proven value, such as DHE-45¹ and NSAIDs,² and preventative medications, such as calcium channel blockers,³ tricyclic antidepressants,⁴ serotonin reuptake inhibitors,⁵ methylergonovine,⁶ and divalproex sodium,⁷ are not available. No one could quarrel with a goal of developing a cost-effective formulary. However, the authors of these formularies have clearly demonstrated their inability to provide even a current, accurate, and adequate formulary by existent standards of care in the treatment of migraine headache. While it is easy to criticize these formularies, it is more difficult to develo a comprehensive list that would satisfy the practitioners' need to provide relief for their patients with a minimum of side effects, and the needs of third-party payers (presumed) to provide quality care at the most economical level.     

Reduction of Migraine Attacks During the Use of Warfarin

Two recent reports on reduction of migraine attacks during treatment with vitamin K antagonists have caught my attention.^1,2 Being a migraine sufferer myself, with considerable improvement of my headache during the use of warfarin, I became interested in the subject. Recently, a young man sought my advice for migraine attacks which had worsened after the withdrawal of warfarin. The previous reports on migraine and warfarin involved elderly patients.^1,2 I report now on these two patients in their 30s, one of them being myself (case 1), who have experienced reduction of migraine attacks during the use of warfarin.     

The Event-Related Potential P300 During Headache-Free Period and Spontaneous Attack in Adult Headache Sufferers

The event-related potential P300 has been studied in 15 migraine without aura sufferers, and in 15 episodic tension-type headache sufferers, during pain-free periods and during spontaneous headache attacks. There were no variations of potential, either of P₃ latency or N₂ -P₃ amplitude, in either group during the interictal period. Similarly, there were no variations of the P300 parameters in the group of tension-type headache subjects during headache attacks; by contrast, a significant elongation of latency ( P <0.01) and an increment of N₂-P₃ wave amplitude ( P <0.002) was observed in the group of migraineurs. The authors discuss the data in accordance with the etiopathogenic theories of migraine and the hypothesis that acetylcholine and norepinephrine are the neurotransmitters able to affect the event-related potential P300, which reflects cerebral activity during sensory information processing and analysis.     

Platelet 3H-imipramine binding and sulphotransferase activity in primary headache

We investigated platelet ³H-imipramine (³H-IMI) binding, a putative peripheral serotonergic marker, and the activity of sulphotransferase (ST), an enzyme involved in the catabolism of catecholamines and phenolic compounds, in 14 patients suffering from migraine without aura (MWoA) and in 10 with tension-type headache (TH), as compared with a group of controls. The possible relationships between the biological parameters and clinical features were also examined. The results showed that the two groups of patients had a lower number of ³H-IMI binding sites and a lower activity of the thermolabile form of ST, which acts preferentially on monoamine substrates, than the healthy controls, with no intergroup differences. Significant correlations between psychopathological rating scales and characteristics of the illness were observed in the patients with TH. The decreased number of platelet ³H-IMI binding sites is suggestive of a presynaptic serotonergic dysfunction and confirms the involvement of 5HT in primary headaches. The reduced ST activity might produce changes in the level of sulphated biogenic amines, including dopamine and tyramine, which might have an additional role in the pathophysiology of some aspects of primary headache.     

Lack of effect of norepinephrine on cranial haemodynamics and headache in healthy volunteers

Stress is a provoking factor for both tension-type headache and migraine attacks. In the present single-blind study, we investigated if stress induced by norepinephrine (NE) could elicit delayed headache in 10 healthy subjects and recorded the cranial arterial responses. NE at a dose of 0.025 µg kg⁻¹ min⁻¹ or placebo was infused for 90 min and the headache was followed for 14 h. Blood flow velocity in the middle cerebral artery (measured with transcranial Doppler) and diameters of the temporal artery and the radial artery (measured with ultrasound) were followed for 2 h. There were no changes in these arterial parameters after NE. In both treatment groups three subjects developed delayed headaches. Thus, stress by NE infusion did not result in delayed headache.     

Relationships Between Food, Wine, and Beer-Precipitated Migrainous Headaches

Five hundred seventy-seven consecutive patients attending the Princess Margaret Migraine Clinic from 1989 to 1991 have been questioned about dietary precipitants of their headaches. Four hundred twenty-nine patients had migraine, of which 16.5% reported that headaches could be precipitated by cheese or chocolate, and nearly always by both. Of the migraine patients, 18.4% reported sensitivity to all alcoholic drinks, while another 11.8% were sensitive to red wine but not to white wine; 28% of the migrainous patients reported that beer would precipitate headaches. There was a definite statistical association between sensitivity to cheese/chocolate and to red wine ( P <0.001) and also to beer ( P <0.001), but none between diet sensitivity and sensitivity to alcoholic drinks in general. None of 40 patients with tension headache (diagnosed by International Headache Society criteria) reported sensitivity to foods, and only one was sensitive to alcoholic drinks. The prevalence of sensitivity among 46 patients with some migrainous features was intermediate between the migraine and tension headache categories. It is concluded that cheese/chocolate and red wine sensitivity, in particular, have closely related mechanisms, in some way related more to migraine than to more chronic tension-type headache, while quite separate mechanisms play a major role in sensitivity to alcoholic drinks in general.     

Deficiency In Serum Ionized Magnesium But Not Total Magnesium In Patients With Migraines. Possible Role Of Ica2+/IMg2+ Ratio

SYNOPSIS
It has been suggested that magnesium (Mg) may play a role in the pathogenesis of headaches. Serum and intracellular measurements of Mg in headache patients have produced inconsistent results. The recent development of an ion-selective electrode for Mg²⁺ allowed precise measurement of serum ionized magnesium (IMg²⁺) in patients with various headache syndromes. Low serum Img²⁺ and a high ICa²⁺/IMg²⁺ ratio were found in 42% of patients having an attack of migraine, but only in 23% of patients with e severe continuous headache. Total serum Mg was normal in both groups of patients. However, in patients with low serum IMg²⁺ total serum Mg was lower than in patients with normal serum IMg²⁺. These results are compatible with the serotonin and vascular concepts of migraine pathogenesis. Low IMg²⁺ and a high ICa²⁺/Img²⁺ would result in cerebral vasospasm and reduced blood flow in the brain. The activity of serotonin receptors can also be affected by changes in IMg²⁺ levels. The finding of a difference in IMg²⁺ levels in two different headache types suggests a possible novel classification of headaches and that migraine patients with a low serum IMg²⁺ or a high ICa²⁺/IMg²⁺ ratio may benefit from Mg supplementation.     

Acephalgic Migraine

SYNOPSIS
Acephalgic migraine is a term used interchangeably with the term migraine equivalents. These terms by definition refer to any migrainous phenomena that may occur in the absence of a migraine headache.¹ Perhaps 20% of migraineurs may experience acephalgic attacks of migraine at one time or another. The idea that various symptoms can occur in the absence of any headache has been noted for hundreds of years, but very little has been written about this condition recently. Some people do not believe the symptoms that are often classified as migraine equivalents are in actuality part of the migraine syndrome. Because there is as yet no specific test for migraine, there is no proof that these various symptoms are due to the same neurovascular dysfunction we know as migraine. The diagnosis of migraine is based only on the patient's history and the exclusion of other diagnoses. It is not unusual for a headache patient to see several headache "specialists" and be given different diagnoses.
Some prefer the term "migraine accompaniments" for neurological or visual symptoms occurring with or without a headache.² The aura of the classic migraine attack may linger into the painful phase and thus "accompany" rather than just precede the headache. At times, symptoms typical of the aura may occur and may not be followed by a headache (acephalgic migraine). The term "complicated migraine"should probably be reserved for those neural and/or visual symptoms that outlast the headache by at least 24 hours and should not be used when referring to symptoms of shorter duration which may accompany the headache or which occur in the absence of migraine headache. Although non-visual migraine equivalents are not nearly as common as visual symptoms, it is important to recognize the fact that migraine may account for almost any recurrent, transient, episodic organ dysfunction.     

Responsiveness of non-IHS migraine and tension-type headache to sumatriptan

In a long-term efficacy and satiety study, 424 patients were treated with sumatriptan (6 mg sc) for 1,904 migraine attacks. The patients were diagnosed with migraine based on IHS criteria but individual migraine attacks treated in the study were physician diagnosed; not necessarily required to meet IHS criteria. A re-analysis of the treatment response to open label sumatriptan (6 mg sc) indicated that 43 patients had treated at least one migraine that fulfilled IHS criteria for tension-type headache. Analysis of this population revealed they treated 232 headaches. Of these headaches, 114 were classified per IHS criteria as migraine; 76 as tension-type; and 42 as. non-IHS migraine (not classifiable as IHS migraine or IHS tension-type headache). Of the 114 migraines a positive response to sumatriptan occurred in 109 (96%) cases; of the 76 tension-types, 73 responded to sumatriptan (97%); of the 42 non-IHS migraine, 40 (95%) responded to sumatriptan. An equivalent response to sumatriptan among three diagnostic groups of headache supports the concept of a common biologic mechanism involving 5HT₁ receptors that spans a range of clinical presentations.     

Platelet serotonin in patients with analgesic-induced headache

The purpose of this study was to investigate the role of serotonin (5HT) in patients with analgesic-induced headache (AIH). We estimated platelet 5HT concentration in patients with AIH, migraine patients and non- headache controls, by using high performance liquid chromatography with electrochemical detection. Our results revealed a significant decrease ( p < 0.00 ) in platelet 5HT content in patients with AIH as compared to migraine patients and non-headache controls (221.8 ± 30.7, 445.3 ± 37.4 and 467.2 ± 38.5 ng/10⁹ platelets, respectively). In contrast, a difference of lesser statistical significance ( p =0.022) was observed in platelet 5HT content after incubation with excess 5HT (1940.0 ± 195.1, 2610.0 ± 173.1 and 2560 + 165.2 ng/10⁹ platelets for patients with AIH, migraine patients and non-headache controls, respectively). These data suggest that analgesic-induced suppression of 5HT uptake may interfere with the function of the pain modulatory system in the brainstem. Although the process by which analgesics interfere with this system is as vet unknown, it is possible that it may not be entirely due to defective 5HT uptake mechanisms.     

Office-Based Treatment of Acute Migraine With Dihydroergotamine Mesylate

SYNOPSIS
The Regional Migraine Field Trial assessed the efficacy and safety of dihydroergotamine mesylate (D.H.E. 45 ^(r) ) for migraine in the office setting. Patients were admitted to the study provided they met the International Headache Society definition of migraine with or without aura. Thirty-eight neurologists enrolled 311 patients (274 women and 37 men) between the ages of 13 and 70 years in this open-design study. Ninety-five percent of the patients had moderate or severe headache pain at entry, and 62% had nausea. All patients received a single intramuscular injection of D.H.E. 45 ^(r) 1 mg. A second intramuscular injection of 1 mg was given 60 minutes after the first injection, if needed. An antiemetic was administered concomitantly with D.H.E. 45 ^(r) , if needed. Rescue therapy was given at the investigators' discretion. Efficacy was judged by the relief of pain, patients' ability to function, need for a second injection, need for rescue medication, and need for an antiemetic. At 30 and 60 minutes, 46% and 72% of patients had only mild or no head pain, respectively. At 24 hours, 77% of all patients had mild or no head pain. D.H.E. 45 ^(r) also improved functional ability. At 30 and 60 minutes, 58% and 75% of patients had only mild or no disability, respectively. At 24 hours, 81% had mild or no impairment. Nausea was present in 62% of patients at the outset, 40% of patients at 30 minutes, and 30% at 60 minutes. An antiemetic was given to 43% of patients at the outset. The presence of nausea was similar whether or not patients received an antiemetic. Rescue medication was needed for 11% of patients, and adverse events were reported by 9%. In conclusion, D.H.E. 45 ^(r) is effective therapy for acute migraine. A second dose provides additional relief, if needed.     

Precipitating and Aggravating Factors of Migraine Versus Tension-type Headache

OBJECTIVE: We conducted the present study to determine whether there are headache precipitating and aggravating factors that differentiate migraine from tension-type headache and headache precipitating and aggravating factors that differentiate tension-type headache from migraine. METHODS: We interviewed 38 patients with migraine and 17 patients with tension-type headache (diagnosed using International Headache Society criteria) by telephone, using a questionnaire. The questionnaire inquired about the following precipitating and aggravating headache factors: (1) physical activity, (2) straining, (3) bending over, (4) stress/tension, (5) coughing/sneezing, (6) fatigue, (7) reading, (8) driving, (9) lack of sleep, (10) specific foods/drinks, (11) alcohol, (12) not eating on time, (13) smoke, (14) smell, (15) light, (16) noise, (17) menstruation, and (18) weather. RESULTS: The most common precipitating factors acknowledged by both groups of patients were stress/tension, not eating on time, fatigue, and lack of sleep. Weather, smell, smoke, and light were the precipitating factors that differentiated migraine from tension-type headache. Excluding those factors that are part of the International Headache Society migraine diagnosis, the aggravating factors were straining, bending over, and smell. We found no precipitating or aggravating factors differentiating tension-type headache from migraine. CONCLUSION: Apparently there are precipitating and aggravating factors differentiating migraine from tension-type headache but not vice versa. It is interesting that three of the migraine-specific precipitating factors (ie, weather, smell, and smoke) involve the nose/sinus system, suggesting a greater significance of this system in headache than is generally considered.     

Exteroceptive suppression of temporal muscle activity is normal in chronic tension-type headache and not related to actual headache state

The aim of the present study was to compare the late exteroceptive suppression period (ES₂) of temporalis muscle activity between patients with chronic tension-type headache and healthy controls, and to investigate the influence, if any, of actual headache on ES₂. ES₂ was recorded in 55 patients and in 55 controls with a previously evaluated methodology and analysed by a blinded observer. The first 20 patients were randomly studied on 2 additional days, 1 day with and 1 day without headache. The duration of ES₂ did not differ between patients and controls and did not differ on days with headache compared with days without headache. ES₂ duration was not related to the frequency of headache, headache intensity, age, pericranial muscle tenderness or electrical pain threshold. Our results strongly indicate that ES₂ is normal in chronic tension-type headache and therefore may not be related to the pathophysiology of this disorder.     

Effect of adrenomedullin on the cerebral circulation: relevance to primary headache disorders

Adrenomedullin (ADM) is closely related to calcitonin gene-related peptide, which has a known causative role in migraine. Animal studies have strongly suggested that ADM has a vasodilatory effect within the cerebral circulation. For these reasons, ADM is also likely to be involved in migraine. However, the hypothetical migraine-inducing property and effect on human cerebral circulation of ADM have not previously been investigated. Human ADM (0.08 µg kg⁻¹ min⁻¹) or placebo (saline 0.9%) was administered as a 20-min intravenous infusion to 12 patients suffering from migraine without aura in a crossover double-blind study. The occurrence of headache and associated symptoms were registered regularly 24 h post infusion. Cerebral blood flow (CBF) was measured by ¹³³Xenon single-photon emission computed tomography, mean blood flow velocity in the middle cerebral artery (V_MCA) by transcranial Doppler and the diameter of peripheral arteries by transdermal ultrasound (C-scan). ADM did not induce significantly more headache or migraine compared with placebo ( P  = 0.58). CBF was unaffected by ADM infusion (global CBF, P  = 0.32 and rCBF_MCA, P  = 0.38) and the same applied for the V_MCA ( P  = 0.18). The superficial temporal artery dilated compared with placebo ( P  < 0.001), and facial flushing was seen after ADM administration ( P  = 0.001). In conclusion, intravenous ADM is not a mediator of migraine headache and does not dilate intracranial arteries.     

Delayed migraine-like headache in healthy volunteers after a combination of acetazolamide and glyceryl trinitrate

Glyceryl trinitrate (GTN) is a pro-drug dissociating nitric oxide throughout the body. It dilates cephalic arteries without increasing cerebral blood flow (CBF). GTN induces headache in healthy volunteers and migraine attacks in migraineurs. Acetazolamide (Az) increases CBF but does not dilate cerebral arteries. The hypothesis tested here was that Az, by dilating cerebral arterioles but not arteries and thereby decreasing pulsatile stretching of the wall of the large arteries and their perivascular sensory nerves, would reduce or prevent the GTN-induced headache We tested this hypothesis in 14 healthy volunteers. In a randomized, double-blind, cross-over study, they were pretreated with Az or placebo followed on both study days by a GTN infusion of 0.5 µg kg⁻¹ min⁻¹ for 20 min. Headache was scored on a verbal rating scale and a headache diary was kept for 12 h. Mean blood velocity of the middle cerebral artery was measured (transcranial Doppler). Our hypothesis was disproved, as Az did not decrease GTN-induced headache. Unexpectedly but interestingly, GTN combined with Az induced more delayed headache than GTN alone. Furthermore, a migraine-like headache was observed in three volunteers, who did not develop migraine after GTN alone. The fact that a suitable pharmacological intervention may trigger migraine in individuals with no prior migraine may suggest that the ability to develop migraine without aura is a quantitative genetic trait.     

Trigger factors of migraine and tension-type headache: experience and knowledge of the patients

The objective was to examine potential trigger factors of migraine and tension-type headache (TTH) in clinic patients and in subjects from the population and to compare the patients’ personal experience with their theoretical knowledge. A cross-sectional study was carried out in a headache centre. There were 120 subjects comprising 66 patients with migraine and 22 with TTH from a headache outpatient clinic and 32 persons with headache (migraine or TTH) from the population. A semistructured interview covering biographic data, lifestyle, medical history, headache characteristics and 25 potential trigger factors differentiating between the patients’ personal experience and their theoretical knowledge was used. The most common trigger factors experienced by the patients were weather (82.5%), stress (66.7%), menstruation (51.4%) and relaxation after stress (50%). The vast majority of triggers occurred occasionally and not consistently. The patients experienced 8.9±4.3 trigger factors (range 0–20) and they knew 13.2±6.0 (range 1–27). The number of experienced triggers was smallest in the population group (p=0.002), whereas the number of triggers known did not differ in the three study groups. Comparing theoretical knowledge with personal experience showed the largest differences for oral contraceptives (65.0 vs. 14.7%, p<0.001), chocolate (61.7 vs. 14.3%, p>0.001) and cheese (52.5 vs. 8.4%, p<0.001). In conclusion, almost all trigger factors are experienced occasionally and not consistently by the majority of patients. Subjects from the population experience trigger factors less often than clinic patients. The difference between theoretical knowledge and personal experience is largest for oral contraceptives, chocolate and cheese.